On August 7, 2017 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical-stage pharmaceutical company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported the initiation of a randomized Phase 2 trial of CB-839, the company’s glutaminase inhibitor, combined with AFINITOR (everolimus)‎ in patients with clear cell renal cell carcinoma (Press release, Calithera Biosciences, AUG 7, 2017, View Source [SID1234520057]).

“Despite the advances in the treatment of renal cell carcinoma, there remains significant unmet need for patients who have progressed following treatment with an anti-PD1 and/or tyrosine kinase inhibitors,” said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. “The initiation of this study marks an important milestone for our company, as it is the first randomized trial of CB-839 that we believe has the potential for U.S Food and Drug Administration (FDA) registration and approval. In recognition of the lack of treatment options available to patients with renal cell carcinoma, the FDA has granted Fast Track Designation to CB-839 in this setting.”

The randomized, double-blind, placebo controlled trial is designed to evaluate the safety and efficacy of CB-839 in combination with everolimus versus placebo with everolimus in approximately 250 patients with metastatic, clear cell renal cell carcinoma (RCC) patients who have been treated with at least two prior lines of systemic therapy including a VEGFR-targeting tyrosine kinase inhibitor and at least one of either CABOMETYX (cabozantinib) or an active PD-1/PD-L1 inhibitor. Patients will be randomized in a 2:1 ratio. The primary endpoint is progression free survival assessed by an independent review committee; overall survival will be assessed as a secondary endpoint. The multicenter, international study will be conducted at multiple sites in the United States, Europe and Canada. Clinical trial sites have been activated and the study is open for enrollment. For a listing of clinical sites and additional details about the clinical trial, please see www.clinicaltrials.gov (NCT03163667).

CB-839 takes advantage of the pronounced dependency many cancers have on the nutrient glutamine for growth and survival. CB-839 inhibits glutaminase, an enzyme required by cancer cells to utilize glutamine effectively, resulting in inhibition of tumor growth. In 2017, RCC is estimated to be diagnosed in approximately 63,990 people in the United States, according to the National Cancer Institute. Clear cell is the most common form of kidney cancer, comprising 70-75% of cases. Most patients with clear cell RCC lack the tumor suppressor gene VHL, making them more dependent on glutamine due to a loss of ability to make fatty acids from glucose1,2,3. Since the mTOR inhibitor everolimus impairs the use of glucose by cancer cells, the combination of CB-839 with everolimus induces dual metabolic inhibition.